protein kinase C-iota (PRKCI, DXS1179E)
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Function
- Ca+2-independent, phospholipid-dependent
- serine/threonine kinase
- may play a role in the secretory response to nutrients
- involved in cell polarization processes formation of epithelial tight junctions
- implicated in activation of several signaling pathways including Ras, c-Src & NF-kappa-B pathways
- functions in both pro- & anti-apoptotic pathways
- functions in the RAC1/ERK signaling required for transformed growth
- role in microtubule dynamics through interaction with RAB2 & GAPDH & recruitment to vesicular tubular clusters (VTCs)
- forms a complex with SQSTM1 & MP2K5 (putative)
- interacts directly with SQSTM1 (probable
- interacts with IKBKB
- interacts with PARD6A, PARD6B & PARD6G
- part of a quaternary complex containing aPKC, PARD3, a PARD6 protein (PARD6A, PARD6B or PARD6G) & a GTPase protein (CDC42 or RAC1)
- part of a complex with LLGL1 & PARD6B
- interacts with CENTA1
- interaction with SMG1, through the ZN-finger domain, activates the kinase activity
- interacts with CDK7
- forms a complex with RAB2 & GAPDH involved in recruitment onto the membrane of vesicular tubular clusters (VTCs)
- might be a target for novel lipid activators that are elevated during nutrient-stimulated insulin secretion
- two specific sites
- Thr-403 (activation loop of the kinase domain)
- Thr-555 (turn motif) need to be phosphorylated for its full activation (putative)
- atypical PCKs are not regulated by diacylglycerol, phorbol esters nor Ca+2
- on neuronal growth factor (NGF) stimulation, phosphorylated by Src on Tyr-256, Tyr-271 & Tyr-325
- phosphorylation on Tyr-256 facilitates binding to KPNB1/ importin-beta regulating entry of PRKCI into the nucleus
- phosphorylation on Tyr-325 is important for NF-kappa-B stimulation
Structure
- OPR domain mediates interaction with SQSTM1
- C1 domain does not bind diacylglycerol (DAG)
- belongs to the protein kinase superfamily, AGC Ser/Thr protein kinase family, PKC subfamily
- contains 1 AGC-kinase C-terminal domain
- contains 1 OPR domain
- contains 1 phorbol-ester/DAG-type Zn+2 finger
- contains 1 protein kinase domain
Compartment
- cytoplasm, membrane, endosome, nucleus
- transported into the endosome through interaction with SQSTM1/p62
- after phosphorylation by cSrc, transported into the nucleus through interaction with KPNB1
- colocalizes with CDK7 in the cytoplasm & nucleus
- vesicular tubular clusters
- transported to VTCs through interaction with Rab2
Expression
- expressed in lung & brain > other tissues including pancreatic islets
Pathology
- PRKCI is highly expressed in non-small cell lung cancers